Determining tumor origin

Abstract

The disclosure provides methods for the use of gene expression measurements to classify or identify among 54 cancer types in samples obtained from a subject in a clinical setting, such as in cases of formalin fixed, paraffin embedded (FFPE) samples.

1 - 17 . (canceled) 
     
     
         18 . A method of treating or altering treatment of a human subject having a tumor based on a tumor type classification of a plurality of tumor types comprising two or more of breast adenocarcinoma, gastro-esophageal adenocarcinoma, adrenal-cortical tumor, tumor of the salivary gland, squamous cell carcinoma of the neck, neuroendocrine-pancreas cancer, merkel cell carcinoma, lung carcinoid, primitive neuroectodermal tumor, sex cord stromal tumor, thymic carcinoma/thymoma, adenocarcinoma of urinary bladder, and squamous cell carcinoma of urinary bladder said method comprising
 obtaining or having obtained a tumor cell-containing sample from the human subject;   producing or having produced an expression profile of transcribed sequences, wherein producing or having produced the expression profile comprises:
 (i) producing or having produced cDNA copies of the transcribed sequences, which comprise 50 or more transcribed sequences of a set of 87 transcribed sequences, from cells in the tumor cell-containing sample, wherein at least 14 of the transcribed sequences consist of a portion of each of genes AF301598 (EMX2), AW473119 (ESR1), BC006537 (HOXA9), BF437393 (HOXB8), BC001293 (HOXC10), AW194680 (HOXD11), A1804745 (IRX3), AK025181 (ISX), X69699 (PAX8), BF446419 (PCANAP6), NM_006115 (PRAME), BC006819 (S100P), AK027147 (TITF1), and A1632869 (UPK1B), and wherein at least 36 of the transcribed sequences consist of a portion of each of 36 genes selected from the group consisting of AA456140, AA745593, AA765597, AA782845, AA865917, AA946776, AA993639, AB038160, AF104032, AF133587, AF332224, A1041545, A1147926, A1309080, A1341378, A1457360, A1620495, A1683181, A1685931, A1802118, A1952953, A1985118, AJ000388, AK054605, AL023657, AL039118, AL110274, AL157475, AW118445, AW291189, AW298545, AW445220, AY033998, BC000045, BC001504, BC001639, BC002551, BC004331, BC004453, BC005364, BC006881, BC008764, BC008765, BC009084, BC009237, BC010626, BC011949, BC012926, BC013117, BC015754, BC017586, 6E552004, 6E962007, BF224381, BF592799, B1493248, H05388, H07885, H09748, M95585, N64339, NM_000065, NM_001337, NM_003914, NM_004062, NM_004063, NM_004496, NM_019894, NM_033229, R15881, R45389, R61469, and X96757; 
 (ii) amplifying or having amplified the cDNA copies to produce amplified molecules; 
 (iii) determining or having determined expression levels of each of the 50 or more transcribed sequences of the set of 87 transcribed sequences in the tumor cell-containing sample; and 
 (iv) comparing or having compared the expression levels of the 50 or more transcribed sequences of the set of 87 transcribed sequences in the tumor cell-containing sample to expression levels of the same transcribed sequences in the plurality of tumor types, to produce the expression profile, wherein at least 25% of the transcribed sequences in the expression profile are non-correlated with any of the plurality of tumor types, and wherein the same at least 25% of the transcribed sequences are not normalization genes; 
   classifying or having classified the tumor cell-containing sample as containing or not containing tumor cells of a tumor type in the plurality of tumor types based on the expression profile, thus producing a tumor type classification; and   treating or altering treatment of the subject based on the tumor type classification.   
     
     
         19 . The method of  claim 18 , wherein the plurality comprises adrenal-cortical tumor, tumor of the salivary gland, squamous cell carcinoma of the neck, neuroendocrine-pancreas cancer, merkel cell carcinoma, lung carcinoid, primitive neuroectodermal tumor, sex cord stromal tumor, thymic carcinoma/thymoma, adenocarcinoma of urinary bladder, and squamous cell carcinoma of urinary bladder. 
     
     
         20 . The method of  claim 18 , wherein the plurality comprises adrenal-cortical tumor, adrenal pheochromocytoma, tumor of the brain, adenocarcinoma of breast, cervical adenocarcinoma, cervical squamous cell carcinoma, cholangiocarcinoma, endometrial adenocarcinoma, esophageal squamous cell carcinoma, gastrointestinal stromal tumor, adenocarcinoma of gallbladder, gastro-esophageal adenocarcinoma, seminomatous germ cell tumor, nonseminomatous germ cell tumor, tumor of the salivary gland, squamous cell carcinoma-of the neck, colorectal adenocarcinoma, small intestine adenocarcinoma, clear cell renal cell carcinoma, chromophobe renal cell carcinoma, papillary renal cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, lymphoma, melanoma, meningioma, mesothelioma, small/large cell neuroendocrine lung cancer, neuroendocrine-pancreas cancer, merkel cell carcinoma, gastrointestinal carcinoid, lung carcinoid, clear cell adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, serous adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, malignant fibroushistiocytoma, primitive neuroectodermal tumor, leiomyosarcoma, liposarcoma, osteosarcoma, synovial sarcoma, sex cord stromal tumor, basal cell carcinoma, skin squamous cell carcinoma, thymic carcinoma/thymoma, follicular/papillary carcinoma, medullary carcinoma, transitional cell carcinoma, adenocarcinoma of bladder, and squamous cell carcinoma of bladder. 
     
     
         21 . The method of  claim 18 , wherein all the expression levels are or have been determined by use of a microarray. 
     
     
         22 . The method of  claim 18 , wherein the amplifying or having amplified comprises amplification of all or part of the transcribed sequences, or reverse transcription and labeling RNA corresponding to the transcribed sequences. 
     
     
         23 . The method of  claim 22 , wherein the amplification comprises linear RNA amplification or quantitative PCR. 
     
     
         24 . The method of  claim 23 , wherein the amplification is quantitative PCR amplification of at least 50 nucleotides of the transcribed sequences. 
     
     
         25 . The method of  claim 18 , wherein the tumor cell-containing sample is a formalin fixed, paraffin embedded (FFPE) sample. 
     
     
         26 . The method of  claim 18 , wherein at least 50% of the transcribed sequences in the expression profile are non-correlated with any of the plurality of tumor types, wherein the same at least 50% of the transcribed sequences are not normalization genes. 
     
     
         27 . The method of  claim 18 , wherein at least 75% of the transcribed sequences in the expression profile are non-correlated with any of the plurality of tumor types, wherein the same at least 75% of the transcribed sequences are not normalization genes. 
     
     
         28 . The method of  claim 18 , wherein at least 85% of the transcribed sequences in the expression profile are non-correlated with any of the plurality of tumor types, wherein the same at least 85% of the transcribed sequences are not normalization genes. 
     
     
         29 . The method of  claim 18 , wherein at least 90% of the transcribed sequences in the expression profile are non-correlated with any of the plurality of tumor types, wherein the same at least 90% of the transcribed sequences are not normalization genes. 
     
     
         30 . A kit comprising:
 polynucleotide probes or primers for 50 or more transcribed sequences of a set of 87 transcribed sequences,   (ii) an antibody,   (iii) a label,   (iv) a means of detecting a label,   (v) buffers and reagents,   (vi) an array, and   (vii) tubes.   
     
     
         31 . The kit of  claim 30 , wherein the means of detecting a label comprises an enzyme, substrates for enzymatic labels, filter sets to detect fluorescent labels, or secondary labels, wherein secondary labels comprise a sheep anti-mouse-HRP.